title: Influenza A virus interacts extensively with the cellular SUMOylation system during infection.
abstract: SUMOylation, the post-translational conjugation of the Small Ubiquitin-like MOdifier (SUMO) to a target protein, regulates a wide array of cellular processes and plays important roles for numerous viruses during infection. However, the relevance of the cellular SUMOylation system for influenza virus infection remains mostly unexplored. We previously reported that the non-structural protein of influenza A virus NS1 is a bona fide SUMO target. Here we determine that at least four additional influenza virus proteins, namely PB1, NP, M1, and NS2, are also authentic SUMO targets, and provide data supporting that PB1, NP, and M1 are SUMOylated during viral infection. The functional relevance of SUMOylation for these proteins is supported by the observation that, despite no apparent changes in the cellular levels of the E1 and E2 SUMO enzymes, influenza viral infection leads to a global increase in cellular SUMOylation. This increase, characterized by the appearance of two new SUMOylated proteins of ∼70kDa and ∼52kDa of molecular weight, is dependent upon viral replication and cannot be recreated by interferon stimulation alone. Altogether, these observations indicate that influenza A virus interacts extensively with the cellular SUMOylation system during infection and suggest that SUMOylation plays an important role during influenza virus infection, potentially contributing to the functional diversity exhibited by influenza viral proteins.
authors.affiliation: Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA.
authors.forename: Sangita
authors.initials: S
authors.lastname: Pal
authors.forename: Andres
authors.initials: A
authors.lastname: Santos
authors.forename: Juan M
authors.initials: JM
authors.lastname: Rosas
authors.forename: Joshua
authors.initials: J
authors.lastname: Ortiz-Guzman
authors.forename: Germán
authors.initials: G
authors.lastname: Rosas-Acosta
mesh_terms: D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins; D014764:Viral Proteins